PT533280E - Novas utilizacoes medicas para antagonistas de taquiquinina - Google Patents
Novas utilizacoes medicas para antagonistas de taquiquinina Download PDFInfo
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- PT533280E PT533280E PT92202831T PT92202831T PT533280E PT 533280 E PT533280 E PT 533280E PT 92202831 T PT92202831 T PT 92202831T PT 92202831 T PT92202831 T PT 92202831T PT 533280 E PT533280 E PT 533280E
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919120172A GB9120172D0 (en) | 1991-09-20 | 1991-09-20 | Chemical compounds |
| GB929202839A GB9202839D0 (en) | 1992-02-11 | 1992-02-11 | Chemical compounds |
| GB929204151A GB9204151D0 (en) | 1992-02-27 | 1992-02-27 | Medicaments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT533280E true PT533280E (pt) | 2001-01-31 |
Family
ID=27265859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT92202831T PT533280E (pt) | 1991-09-20 | 1992-09-16 | Novas utilizacoes medicas para antagonistas de taquiquinina |
Country Status (14)
| Country | Link |
|---|---|
| US (7) | US5360820A (OSRAM) |
| EP (4) | EP0916346A3 (OSRAM) |
| JP (1) | JP3020757B2 (OSRAM) |
| KR (1) | KR100233323B1 (OSRAM) |
| AT (1) | ATE195867T1 (OSRAM) |
| AU (1) | AU657996B2 (OSRAM) |
| CA (1) | CA2078578C (OSRAM) |
| DE (1) | DE69231395T3 (OSRAM) |
| DK (1) | DK0533280T4 (OSRAM) |
| ES (1) | ES2149767T5 (OSRAM) |
| GR (1) | GR3034682T3 (OSRAM) |
| IL (1) | IL103214A (OSRAM) |
| PT (1) | PT533280E (OSRAM) |
| TW (1) | TW311139B (OSRAM) |
Families Citing this family (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0733386B2 (ja) * | 1991-05-31 | 1995-04-12 | フアイザー・インコーポレイテツド | キヌクリジン誘導体 |
| EP0916346A3 (en) | 1991-09-20 | 2000-12-06 | Glaxo Group Limited | NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis |
| US5444074A (en) * | 1992-04-15 | 1995-08-22 | Merck Sharp & Dohme Limited | Piperidine tachykinin receptor antagonists |
| US5719147A (en) * | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| US6048859A (en) * | 1992-06-29 | 2000-04-11 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| US5637699A (en) * | 1992-06-29 | 1997-06-10 | Merck & Co., Inc. | Process for preparing morpholine tachykinin receptor antagonists |
| GB9216911D0 (en) * | 1992-08-10 | 1992-09-23 | Merck Sharp & Dohme | Therapeutic agents |
| US5837711A (en) * | 1992-10-28 | 1998-11-17 | Pfizer Inc. | Substituted quinuclidines as substance P antagonists |
| DE69307340T2 (de) * | 1992-11-12 | 1997-04-24 | Pfizer | Chinuclidin derivat als substanz p antagonist |
| FR2700472B1 (fr) | 1993-01-19 | 1995-02-17 | Rhone Poulenc Rorer Sa | Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2. |
| GB9305593D0 (en) * | 1993-03-18 | 1993-05-05 | Smithkline Beecham Plc | Pharmaceuticals |
| GB9305718D0 (en) * | 1993-03-19 | 1993-05-05 | Glaxo Group Ltd | Medicaments |
| US5496833A (en) * | 1993-04-13 | 1996-03-05 | Merck Sharp & Dohme Limited | Piperidine tachykinin receptor antagonists |
| DE69404306T2 (de) | 1993-05-28 | 1997-10-30 | Pfizer | Verfahren zur herstellung und optischen auflösung von 2-phenyl-3-aminopiperidine |
| US5393762A (en) * | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
| FR2710842B1 (fr) * | 1993-10-07 | 1995-11-24 | Rhone Poulenc Rorer Sa | Nouvelle application thérapeutique de dérivés de perhydroisoindole. |
| EP0653208A3 (en) * | 1993-11-17 | 1995-10-11 | Pfizer | Substance P antagonists for the treatment or prevention of sunburn. |
| US5610165A (en) * | 1994-02-17 | 1997-03-11 | Merck & Co., Inc. | N-acylpiperidine tachykinin antagonists |
| TW385308B (en) * | 1994-03-04 | 2000-03-21 | Merck & Co Inc | Prodrugs of morpholine tachykinin receptor antagonists |
| US5491140A (en) * | 1994-06-30 | 1996-02-13 | Eli Lilly And Company | Naphthyl tachykinin receptor antagonists to treat physiological conditions |
| CZ288434B6 (en) | 1994-07-12 | 2001-06-13 | Lilly Co Eli | Dihydrochloride trihydrate of (R)-3-(1H-indol-3-yl)-1-[N-(2-methoxybenzyl)acetylamino]-2-[N-/2-(4-piperid-1-yl)piperid-1-yl)acetyl/-amino]propane, pharmaceutical preparation in which it is comprised and use thereof |
| MX9703483A (es) * | 1994-11-10 | 1997-08-30 | Pfizer | Antagonistas del receptor de nk-1 para el tratamiento de trastornos oculares. |
| US5576317A (en) * | 1994-12-09 | 1996-11-19 | Pfizer Inc. | NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis |
| JPH10510540A (ja) | 1994-12-12 | 1998-10-13 | オメロス メディカル システムズ，インコーポレーテッド | 灌注用溶液並びに疼痛、炎症及びけいれんの抑制法 |
| WO1996019233A2 (en) * | 1994-12-12 | 1996-06-27 | Omeros Medical Systems, Inc. | Irrigation solution and method for inhibition of pain, inflammation and spasm |
| GB9426102D0 (en) * | 1994-12-23 | 1995-02-22 | Merck Sharp & Dohme | Pharmacuetical compositions |
| US5565568A (en) * | 1995-04-06 | 1996-10-15 | Eli Lilly And Company | 2-acylaminopropanamides as tachykinin receptor antagonists |
| AU5966196A (en) * | 1995-06-08 | 1997-01-09 | Eli Lilly And Company | Methods of treating cold and allergic rhinitis |
| WO1996041631A1 (en) * | 1995-06-09 | 1996-12-27 | Eli Lilly And Company | Methods of treating cold and allergic rhinitis |
| GB9513972D0 (en) * | 1995-07-08 | 1995-09-06 | Merck Sharp & Dohme | Pharmaceutical compositions |
| FR2738742B1 (fr) * | 1995-09-19 | 1997-11-14 | Oreal | Utilisation d'au moins une eau thermale de vichy en tant qu'antagoniste de substance p |
| TW458774B (en) | 1995-10-20 | 2001-10-11 | Pfizer | Antiemetic pharmaceutical compositions |
| GB9524104D0 (en) * | 1995-11-24 | 1996-01-24 | Smithkline Beecham Spa | Novel compounds |
| AU714542B2 (en) * | 1996-06-26 | 2000-01-06 | Warner-Lambert Company | Use of a tachykinin antagonist for the manufacture of a medicament for the treatment of emesis |
| EP0912174B1 (en) * | 1996-07-17 | 2004-04-28 | MERCK & CO., INC. | Alteration of circadian rhythmicity with non-peptidal neurikinin-1 receptor antagonists |
| MX9706944A (es) * | 1996-09-12 | 1998-08-30 | Pfizer | Quinuclidinas sustituidas con tetrazolilo como antagonistas de la sustancia p. |
| US6117855A (en) | 1996-10-07 | 2000-09-12 | Merck Sharp & Dohme Ltd. | Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent |
| US5773458A (en) * | 1996-10-30 | 1998-06-30 | American Home Products Corporation | 1-azabicycloheptane derivatives |
| US6613765B1 (en) | 1996-12-02 | 2003-09-02 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating major depressive disorders |
| US6114315A (en) * | 1996-12-02 | 2000-09-05 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating major depressive disorders with anxiety |
| AU731349B2 (en) * | 1996-12-02 | 2001-03-29 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating sexual dysfunctions |
| CA2273806A1 (en) * | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating substance use disorders |
| JP2001507678A (ja) * | 1996-12-02 | 2001-06-12 | メルク シヤープ エンド ドーム リミテツド | 運動障害の治療のためのｎｋ−１受容体拮抗薬の使用 |
| AU731672B2 (en) * | 1996-12-02 | 2001-04-05 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating bipolar disorders |
| ATE293975T1 (de) * | 1996-12-02 | 2005-05-15 | Merck Sharp & Dohme | Die verwendung von nk-1 rezeptor antagonisten für die behandlung von kognitiven störungen |
| US6100256A (en) * | 1996-12-02 | 2000-08-08 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptors antagonists for treating schizophrenic disorders |
| US5977104A (en) * | 1996-12-02 | 1999-11-02 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating bipolar disorders |
| US5846973A (en) * | 1997-05-23 | 1998-12-08 | Eli Lilly And Company | Methods of treating pulmonary hypertension |
| WO1999007376A1 (en) * | 1997-08-04 | 1999-02-18 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating mania |
| GB9716463D0 (en) * | 1997-08-04 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic agents |
| HUP0003548A3 (en) | 1997-08-06 | 2002-04-29 | Lilly Co Eli | 2-acylaminopropanamines as tachykinin receptor antagonists and pharmaceutical compositions containing the same |
| BR9811821A (pt) | 1997-08-06 | 2000-08-15 | Lilly Co Eli | 2-acilaminopropanaminas como antagonistas de receptores de taquicinina |
| US6548490B1 (en) | 1997-10-28 | 2003-04-15 | Vivus, Inc. | Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction |
| US6271230B1 (en) | 1997-12-01 | 2001-08-07 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating cognitive disorders |
| US6087348A (en) * | 1997-12-01 | 2000-07-11 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating stress disorders |
| US6156749A (en) * | 1997-12-01 | 2000-12-05 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating movement disorders |
| WO1999059583A1 (en) * | 1998-05-18 | 1999-11-25 | Merck & Co., Inc. | Method for treating or preventing chronic nonbacterial prostatitis and prostatodynia |
| GB9812662D0 (en) * | 1998-06-11 | 1998-08-12 | Merck Sharp & Dohme | Therapeutic use |
| AU1409100A (en) * | 1998-11-27 | 2000-06-19 | Takeda Chemical Industries Ltd. | Drugs |
| IL133077A0 (en) * | 1999-01-29 | 2001-03-19 | Pfizer Prod Inc | Azithromycin combination for emesis control in dogs |
| GB9923748D0 (en) * | 1999-10-07 | 1999-12-08 | Glaxo Group Ltd | Chemical compounds |
| USRE39921E1 (en) | 1999-10-07 | 2007-11-13 | Smithkline Beecham Corporation | Chemical compounds |
| DK1246806T3 (da) | 1999-11-03 | 2008-06-16 | Amr Technology Inc | Aryl- og heteroarylsubstituerede tetrahydroisoquinoliner og anvendelse deraf til blokering af genoptagelse af norepinefrin, dopsmin og serotonin |
| US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
| GB9927125D0 (en) | 1999-11-16 | 2000-01-12 | Univ Reading The | Placental human neurokinin B precursor |
| TR200302077T4 (tr) * | 1999-11-29 | 2004-01-21 | F. Hoffmann-La Roche Ag | 2-(3,5-Bis-Trifluorometil-fenil)-N-metil-N- (6-morfonil-4-il-4-O-tolil-piridin-3-il)- izobütiramit |
| KR100821410B1 (ko) | 2000-07-11 | 2008-04-10 | 에이엠알 테크놀로지, 인크. | 4-페닐 치환된 테트라하이드로이소퀴놀린 및 이의치료학적 용도 |
| GB0025354D0 (en) * | 2000-10-17 | 2000-11-29 | Glaxo Group Ltd | Chemical compounds |
| EP1205855A3 (en) * | 2000-11-10 | 2006-01-25 | Masae Yanagi | Data managing method, data managing system, data managing apparatus, data handling apparatus, computer program, and recording medium |
| GB0108594D0 (en) * | 2001-04-05 | 2001-05-23 | Glaxo Group Ltd | Chemical compounds |
| WO2003018586A1 (en) * | 2001-08-24 | 2003-03-06 | Pharmacia & Upjohn Company | Substituted-aryl 7-aza[2.2.1]bicycloheptanes for the treatment of disease |
| EP1297826A1 (en) * | 2001-09-27 | 2003-04-02 | Menarini Ricerche S.p.A. | Nasal pharmaceutical compositions containing a NK-2 antagonist |
| GB0203020D0 (en) * | 2002-02-08 | 2002-03-27 | Glaxo Group Ltd | Chemical compounds |
| US7482365B2 (en) * | 2002-02-08 | 2009-01-27 | Glaxo Group Limited | Piperidylcarboxamide derivatives and their use in the treatment of tachykinin-mediated diseases |
| GB0203022D0 (en) * | 2002-02-08 | 2002-03-27 | Glaxo Group Ltd | Chemical compounds |
| US20040001895A1 (en) * | 2002-06-17 | 2004-01-01 | Pfizer Inc. | Combination treatment for depression and anxiety |
| CA2392486A1 (en) | 2002-07-05 | 2002-12-08 | Duchesnay Inc. | Pharmaceutical dosage form bearing pregnancy-friendly indicia |
| RU2228752C1 (ru) * | 2003-03-21 | 2004-05-20 | Государственный научный центр - Институт биофизики | Фармацевтическая композиция, содержащая ондансетрон и бензамид |
| US20040202717A1 (en) | 2003-04-08 | 2004-10-14 | Mehta Atul M. | Abuse-resistant oral dosage forms and method of use thereof |
| AR049419A1 (es) * | 2004-03-03 | 2006-08-02 | Altana Pharma Ag | Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo |
| CN1926113B (zh) * | 2004-03-10 | 2010-06-23 | 尼科梅德有限责任公司 | 新的酰氨基取代的羟基-6-苯基菲啶化合物及其作为pde4抑制剂的应用 |
| CN103880827B (zh) | 2004-07-15 | 2017-01-04 | 阿尔巴尼分子研究公司 | 芳基和杂芳基取代的四氢异喹啉及其阻断去甲肾上腺素、多巴胺和血清素的重摄取的应用 |
| NZ560232A (en) | 2005-02-25 | 2010-11-26 | Hoffmann La Roche | Tablets with improved drug substance dispersibility |
| WO2006123182A2 (en) | 2005-05-17 | 2006-11-23 | Merck Sharp & Dohme Limited | Cyclohexyl sulphones for treatment of cancer |
| EP1904069B1 (en) | 2005-07-15 | 2018-06-13 | Albany Molecular Research, Inc. | Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
| GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US20090149462A1 (en) * | 2006-08-28 | 2009-06-11 | Hetero Drugs Limited | Process for purification of aprepitant |
| SI2124556T1 (sl) | 2006-10-09 | 2015-01-30 | Charleston Laboratories, Inc. | Farmacevtske sestave |
| US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
| BRPI0806245B1 (pt) | 2007-01-10 | 2022-01-25 | Msd Italia S.R.L. | Compostos de fórmula i e seus usos |
| EP2117538A1 (en) | 2007-01-24 | 2009-11-18 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| WO2008133344A2 (en) * | 2007-04-24 | 2008-11-06 | Takeda Pharmaceutical Company Limited | Piperidine derivative and use thereof |
| AU2008269154B2 (en) | 2007-06-27 | 2014-06-12 | Merck Sharp & Dohme Llc | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
| EP3090743A1 (en) | 2008-01-09 | 2016-11-09 | Charleston Laboratories, Inc. | Pharmaceutical compositions for treating headache and eliminating nausea |
| AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
| US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
| WO2010114780A1 (en) | 2009-04-01 | 2010-10-07 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
| KR20120034644A (ko) | 2009-05-12 | 2012-04-12 | 알바니 몰레큘라 리써치, 인크. | 아릴, 헤테로아릴, 및 헤테로사이클 치환된 테트라하이드로이소퀴놀린 및 이의 용도 |
| WO2010132442A1 (en) | 2009-05-12 | 2010-11-18 | Albany Molecular Reserch, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
| MX2011011900A (es) | 2009-05-12 | 2012-01-20 | Squibb Bristol Myers Co | Formas cristalinas de (s)-7-([1,2,4]triazolo[1,5-a]piridin-6-il)-4 -(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y usos de las misma. |
| EP3311667A1 (en) | 2009-07-08 | 2018-04-25 | Charleston Laboratories, Inc. | Pharmaceutical compositions |
| PE20121172A1 (es) | 2009-10-14 | 2012-09-05 | Merck Sharp & Dohme | Piperidinas sustituidas con actividad en la hdm2 |
| US8518907B2 (en) | 2010-08-02 | 2013-08-27 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA) |
| EP3587574B1 (en) | 2010-08-17 | 2022-03-16 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina) |
| US8883801B2 (en) | 2010-08-23 | 2014-11-11 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors |
| WO2012030685A2 (en) | 2010-09-01 | 2012-03-08 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
| US9242981B2 (en) | 2010-09-16 | 2016-01-26 | Merck Sharp & Dohme Corp. | Fused pyrazole derivatives as novel ERK inhibitors |
| DK2632472T3 (en) | 2010-10-29 | 2018-03-19 | Sirna Therapeutics Inc | RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA) |
| US9351965B2 (en) | 2010-12-21 | 2016-05-31 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as ERK inhibitors |
| US20140046059A1 (en) | 2011-04-21 | 2014-02-13 | Piramal Enterprises Limited | Process for the preparation of morpholino sulfonyl indole derivatives |
| NO2729147T3 (OSRAM) | 2011-07-04 | 2018-02-03 | ||
| WO2013063214A1 (en) | 2011-10-27 | 2013-05-02 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| US20150299696A1 (en) | 2012-05-02 | 2015-10-22 | Sirna Therapeutics, Inc. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
| LT2866797T (lt) | 2012-07-06 | 2020-06-25 | Pharmathen S.A. | Stabili injekuojama neurokinino 1 receptoriaus antagonisto farmacinė kompozicija ir jos gamybos būdas |
| MX2015004041A (es) | 2012-09-28 | 2015-07-06 | Merck Sharp & Dohme | Compuestos novedosos que son inhibidores de erk. |
| EP2925888B1 (en) | 2012-11-28 | 2017-10-25 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
| AR094116A1 (es) | 2012-12-20 | 2015-07-08 | Merck Sharp & Dohme | Imidazopiridinas sustituidas como inhibidores de hdm2 |
| EP2951180B1 (en) | 2013-01-30 | 2018-05-02 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as hdm2 inhibitors |
| EP3041938A1 (en) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Circular polynucleotides |
| US10610532B2 (en) | 2015-08-03 | 2020-04-07 | Leiutis Pharmaceuticals Pvt. Ltd. | Liquid formulations of fosaprepitant |
| US9913853B2 (en) | 2015-11-03 | 2018-03-13 | Cipla Limited | Stabilized liquid fosaprepitant formulations |
| CA3055170A1 (en) | 2016-03-04 | 2017-09-08 | Charleston Laboratories, Inc. | Pharmaceutical compositions |
| US10975084B2 (en) | 2016-10-12 | 2021-04-13 | Merck Sharp & Dohme Corp. | KDM5 inhibitors |
| WO2019038656A1 (en) | 2017-08-21 | 2019-02-28 | Leiutis Pharmaceuticals Pvt, Ltd | NEW TRIPLE COMBINATION FORMULATIONS FOR ANTIEMETIC THERAPY |
| US10947234B2 (en) | 2017-11-08 | 2021-03-16 | Merck Sharp & Dohme Corp. | PRMT5 inhibitors |
| US11098059B2 (en) | 2017-11-08 | 2021-08-24 | Merck Sharp & Dohme Corp. | PRMT5 inhibitors |
| CN111918647A (zh) | 2018-02-26 | 2020-11-10 | 圣拉斐尔医院有限公司 | 用于治疗眼痛的nk-1拮抗剂 |
| WO2020033282A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| WO2020033288A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| US11981701B2 (en) | 2018-08-07 | 2024-05-14 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
| WO2021180885A1 (en) | 2020-03-11 | 2021-09-16 | Ospedale San Raffaele S.R.L. | Treatment of stem cell deficiency |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4048058A (en) * | 1975-08-13 | 1977-09-13 | Standard Oil Company (Indiana) | Methods to be used in reforming processes employing multi-metallic catalysts |
| US4066772A (en) * | 1975-07-21 | 1978-01-03 | Janssen Pharmaceutica N.V. | 1,3-Dihydro-1-[3-(1-piperidinyl)propyl]-2H-benzimidazol-2-ones and related compounds |
| US4175129A (en) * | 1975-07-21 | 1979-11-20 | Janssen Pharmaceutica N.V. | Antiemetic 1-(benzoxazolylalkyl)-piperidine derivatives |
| US4160836A (en) * | 1976-05-17 | 1979-07-10 | Janssen Pharmaceutica N.V. | Antiemetic 1-(benzothiazolylalkyl)piperidine derivatives |
| GB2100259B (en) | 1981-06-13 | 1984-10-31 | Merrell Toraude & Co | Treatment of migraine with tropyl benzoate derivatives |
| DE3445377A1 (de) | 1983-12-23 | 1985-07-04 | Sandoz-Patent-GmbH, 7850 Lörrach | Carbocylische und heterocyclische carbonsaeureester und -amide von ueberbrueckten und nicht ueberbrueckten cyclischen stickstoffhaltigen aminen oder alkoholen |
| US4695578A (en) * | 1984-01-25 | 1987-09-22 | Glaxo Group Limited | 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances |
| GB8401888D0 (en) | 1984-01-25 | 1984-02-29 | Glaxo Group Ltd | Heterocyclic compounds |
| DE3650772T2 (de) * | 1985-04-27 | 2003-04-03 | F. Hoffmann-La Roche Ag, Basel | Derivate von Indazole-3-carboxamide und -3-carboxylsäure |
| GB8516083D0 (en) | 1985-06-25 | 1985-07-31 | Glaxo Group Ltd | Heterocyclic compounds |
| US4910193A (en) | 1985-12-16 | 1990-03-20 | Sandoz Ltd. | Treatment of gastrointestinal disorders |
| DE3687980T2 (de) * | 1986-01-07 | 1993-06-17 | Beecham Group Plc | Indolderivate mit einer azabicyclischen seitenkette, verfahren zu ihrer herstellung, zwischenprodukte und pharmazeutische zusammensetzungen. |
| US4906755A (en) | 1986-11-03 | 1990-03-06 | Merrell Dow Pharmaceuticals Inc. | Esters of hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3-(4H)-one and related compounds |
| US4839465A (en) | 1987-01-20 | 1989-06-13 | Sterling Drug Inc. | Di-(D-tryptophyl and/or tetrahydropyridoindolylcarbonyl)-containing peptide amides and process for preparation thereof |
| FR2610323B1 (fr) | 1987-02-04 | 1989-06-23 | Delalande Sa | Enantiomeres de configuration absolue s de derives amide de l'amino-3 quinuclidine, leur procede de preparation et leur application en therapeutique |
| DE3711335A1 (de) | 1987-04-03 | 1988-10-20 | Merck Patent Gmbh | Aminosaeurederivate |
| US5360800A (en) | 1987-09-03 | 1994-11-01 | Glaxo Group Limited | Tetrahydro-1H-pyrido[4,3-b]indol-1-one derivatives |
| JPH01199575A (ja) | 1988-02-04 | 1989-08-10 | Rikagaku Kenkyusho | 新規なサイクロマルトデキストリン・グルカノトランスフェラーゼ及びその製造法 |
| GB8805269D0 (en) * | 1988-03-04 | 1988-04-07 | Glaxo Group Ltd | Medicaments |
| GB8807246D0 (en) | 1988-03-25 | 1988-04-27 | Merck Sharp & Dohme | Therapeutic agents |
| EP0363085A3 (en) * | 1988-10-03 | 1991-03-27 | Beecham Group Plc | Novel compounds |
| WO1990005525A1 (en) * | 1988-11-23 | 1990-05-31 | Pfizer Inc. | Quinuclidine derivatives as substance p antagonists |
| US4920227A (en) * | 1988-11-29 | 1990-04-24 | Rorer Pharmaceutical Corp. | Benzobicyclic carboxamide 5-HT3 antagonists |
| US5164372A (en) * | 1989-04-28 | 1992-11-17 | Fujisawa Pharmaceutical Company, Ltd. | Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same |
| CA2022886A1 (en) * | 1989-08-08 | 1991-02-09 | Raymond Baker | Substituted pyridines, their preparation, formulations and use in dementia |
| IE77033B1 (en) | 1989-08-16 | 1997-11-19 | Univ Tulane | Substance P antagonists |
| IE903957A1 (en) * | 1989-11-06 | 1991-05-08 | Sanofi Sa | Aromatic amine compounds, their method of preparation and¹pharmaceutical compositions in which they are present |
| FR2654725B1 (fr) * | 1989-11-23 | 1992-02-14 | Rhone Poulenc Sante | Nouveaux derives de l'isoindolone, leur preparation et les compositions pharmaceutiques qui les contiennent. |
| DK0430190T3 (da) | 1989-11-28 | 1995-08-21 | Syntex Inc | Hidtil ukendte tricykliske forbindelser |
| US5232929A (en) | 1990-11-28 | 1993-08-03 | Pfizer Inc. | 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use |
| WO1991009844A1 (en) * | 1990-01-04 | 1991-07-11 | Pfizer Inc. | Substance p antagonists |
| US5321032A (en) | 1990-02-15 | 1994-06-14 | Fujisawa Pharmaceutical Co., Ltd. | Peptide compounds and pharmaceutical compositions thereof |
| DE4007869A1 (de) | 1990-03-13 | 1991-09-19 | Merck Patent Gmbh | Aminosaeurederivate |
| IT1240643B (it) | 1990-05-11 | 1993-12-17 | Mediolanum Farmaceutici Spa | Peptidi biologicamente attivi contenenti in catena 2-alchiltriptofano |
| FI931370A0 (fi) * | 1990-09-28 | 1993-03-26 | Pfizer | Kvaeve innehaollande analoger av icke-aromatiska heterocykliska foereningar med en fusionerad ring |
| GB9023116D0 (en) | 1990-10-24 | 1990-12-05 | Fujisawa Pharmaceutical Co | Peptide compounds,processes for preparation thereof and pharmaceutical composition comprising the same |
| DE4034829A1 (de) | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | Cyclopeptide |
| ATE154354T1 (de) * | 1991-02-11 | 1997-06-15 | Merck Sharp & Dohme | Azabicyclische verbindungen, diese enthaltende pharmazeutische zubereitungen und ihre therapeutische verwendung |
| KR0145432B1 (ko) | 1991-03-26 | 1998-07-15 | 알렌 제이. 스피겔 | 치환된 피페리딘의 입체선택적 제조 방법 |
| WO1993000331A1 (en) | 1991-06-20 | 1993-01-07 | Pfizer Inc. | Fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles |
| TW202432B (OSRAM) | 1991-06-21 | 1993-03-21 | Pfizer | |
| US5629347A (en) | 1991-07-05 | 1997-05-13 | Merck Sharp & Dohme Ltd. | Aromatic compounds, pharmaceutical compositions containing them and their use in therapy |
| EP0916346A3 (en) | 1991-09-20 | 2000-12-06 | Glaxo Group Limited | NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis |
| US5719147A (en) | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| US6048859A (en) | 1992-06-29 | 2000-04-11 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| GB9305718D0 (en) | 1993-03-19 | 1993-05-05 | Glaxo Group Ltd | Medicaments |
| US5393762A (en) | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
| US5576317A (en) * | 1994-12-09 | 1996-11-19 | Pfizer Inc. | NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis |
| JP3503768B2 (ja) * | 1995-01-06 | 2004-03-08 | 関西電力株式会社 | 溝掘削機の制御装置 |
| TW458774B (en) | 1995-10-20 | 2001-10-11 | Pfizer | Antiemetic pharmaceutical compositions |
| ZA985765B (en) | 1997-07-02 | 1999-08-04 | Merck & Co Inc | Polymorphic form of a tachykinin receptor antagonist. |
-
1992
- 1992-09-16 EP EP99200337A patent/EP0916346A3/en not_active Withdrawn
- 1992-09-16 PT PT92202831T patent/PT533280E/pt unknown
- 1992-09-16 EP EP00203202A patent/EP1082959A1/en not_active Withdrawn
- 1992-09-16 DE DE69231395T patent/DE69231395T3/de not_active Expired - Lifetime
- 1992-09-16 DK DK92202831T patent/DK0533280T4/da active
- 1992-09-16 EP EP92202831A patent/EP0533280B2/en not_active Expired - Lifetime
- 1992-09-16 ES ES92202831T patent/ES2149767T5/es not_active Expired - Lifetime
- 1992-09-16 EP EP99200338A patent/EP0919245A3/en not_active Withdrawn
- 1992-09-16 AT AT92202831T patent/ATE195867T1/de active
- 1992-09-18 KR KR1019920017021A patent/KR100233323B1/ko not_active Expired - Lifetime
- 1992-09-18 CA CA002078578A patent/CA2078578C/en not_active Expired - Lifetime
- 1992-09-18 US US07/946,635 patent/US5360820A/en not_active Expired - Lifetime
- 1992-09-18 JP JP4275091A patent/JP3020757B2/ja not_active Expired - Lifetime
- 1992-09-18 AU AU24583/92A patent/AU657996B2/en not_active Expired
- 1992-09-18 IL IL10321492A patent/IL103214A/en not_active IP Right Cessation
- 1992-09-29 TW TW081107713A patent/TW311139B/zh not_active IP Right Cessation
-
1994
- 1994-06-30 US US08/269,079 patent/US5538982A/en not_active Expired - Lifetime
-
1995
- 1995-12-27 US US08/579,294 patent/US5798363A/en not_active Expired - Lifetime
-
1996
- 1996-09-03 US US08/706,836 patent/US6326383B1/en not_active Expired - Fee Related
-
1999
- 1999-05-14 US US09/311,570 patent/US6191139B1/en not_active Expired - Lifetime
-
2000
- 2000-10-26 GR GR20000402369T patent/GR3034682T3/el unknown
-
2001
- 2001-11-05 US US09/985,679 patent/US7214692B2/en not_active Expired - Fee Related
-
2004
- 2004-11-18 US US10/990,462 patent/US7342028B2/en not_active Expired - Fee Related
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